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Sihardo L, Lalisang ANL, Syaiful RA, Putra AB, Mazni Y, Putranto AS, Lalisang TJM. Seizing tumor factors for mortality and survival outcomes following liver resection in Indonesia's hepatocellular carcinoma patients. Ann Hepatobiliary Pancreat Surg 2025; 29:11-20. [PMID: 39734304 PMCID: PMC11830890 DOI: 10.14701/ahbps.24-179] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/21/2024] [Revised: 11/14/2024] [Accepted: 11/19/2024] [Indexed: 12/31/2024] Open
Abstract
Backgrounds/Aims The 3-year mortality rate for hepatocellular carcinoma (HCC) in Indonesia was 94.4%. This underscores a significant health issue in Southeast Asia, particularly in Indonesia due to its large population. This study aimed to characterize the outcomes of liver resection for HCC at a National Referral Center in Indonesia. Methods Between 2010 and 2020, all patients with HCC undergoing liver resection were included as subjects. Variables collected included sex, age, hepatitis status, and tumor's characteristics. Mortality and survival were the primary outcomes of the study. Results Among seventy patients, the mortality rate was 71.4%, with a median overall survival of 19.0 months (95% confidence interval [95%CI]: 6.831.2). Thirty-one patients (44.3%) had extra-large HCC tumors (> 10 cm). Those with extra-large tumors had a lower median survival of 8.0 months. Child-Pugh B and Edmonson-Steiner grade 4 were associated with an increased mortality risk, with unadjusted hazard ratios (HRs) of 2.2 (95%CI: 1.14.3, p = 0.026) and 3.2 (95%CI: 1.37.7, p = 0.011), respectively. Multivariate analysis indicated that Child-Pugh class B significantly increased the risk of mortality, with an adjusted HR of 2.3 (95%CI: 1.05.2, p = 0.046). Conclusions While surgical resection is feasible for tumors of any size, most clinical features are not statistically significantly associated with survival outcomes. The prevalence of extra-large tumors among Indonesian HCC patients highlights the importance of early diagnosis and intervention. Surgical intervention at an earlier stage and with better grade tumors could potentially enhance survival outcomes.
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Affiliation(s)
- Lam Sihardo
- Division of Digestive Surgery, Department of Surgery, Dr. Cipto Mangunkusumo Hospital, Faculty of Medicine Universitas Indonesia, Jakarta, Indonesia
| | - Arnetta Naomi Louise Lalisang
- Division of Digestive Surgery, Department of Surgery, Dr. Cipto Mangunkusumo Hospital, Faculty of Medicine Universitas Indonesia, Jakarta, Indonesia
| | - Ridho Ardhi Syaiful
- Division of Digestive Surgery, Department of Surgery, Dr. Cipto Mangunkusumo Hospital, Faculty of Medicine Universitas Indonesia, Jakarta, Indonesia
| | - Afid Brilliana Putra
- Division of Digestive Surgery, Department of Surgery, Dr. Cipto Mangunkusumo Hospital, Faculty of Medicine Universitas Indonesia, Jakarta, Indonesia
| | - Yarman Mazni
- Division of Digestive Surgery, Department of Surgery, Dr. Cipto Mangunkusumo Hospital, Faculty of Medicine Universitas Indonesia, Jakarta, Indonesia
| | - Agi Satria Putranto
- Division of Digestive Surgery, Department of Surgery, Dr. Cipto Mangunkusumo Hospital, Faculty of Medicine Universitas Indonesia, Jakarta, Indonesia
| | - Toar Jean Maurice Lalisang
- Division of Digestive Surgery, Department of Surgery, Dr. Cipto Mangunkusumo Hospital, Faculty of Medicine Universitas Indonesia, Jakarta, Indonesia
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Xiang D, Fu L, Yang Y, Liu C, He Y. Evaluating the diagnostic accuracy of heat shock proteins and their combination with Alpha-Fetoprotein in the detection of hepatocellular carcinoma: a meta-analysis. BMC Gastroenterol 2024; 24:178. [PMID: 38773451 PMCID: PMC11110180 DOI: 10.1186/s12876-024-03260-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/20/2023] [Accepted: 05/10/2024] [Indexed: 05/23/2024] Open
Abstract
BACKGROUND A growing body of research suggests that heat shock proteins (HSPs) may serve as diagnostic biomarkers for hepatocellular carcinoma (HCC), but their results are still controversial. This meta-analysis endeavors to evaluate the diagnostic accuracy of HSPs both independently and in conjunction with alpha-fetoprotein (AFP) as novel biomarkers for HCC detection. METHODS Pooled statistical indices, including sensitivity, specificity, diagnostic odds ratio (DOR), positive likelihood ratio (PLR), and negative likelihood ratio (NLR) with 95% confidence intervals (CI), were computed to assess the diagnostic accuracy of HSPs, AFP, and their combinations. Additionally, the area under the summary receiver operating characteristic (SROC) curve (AUC) was determined. RESULTS A total of 2013 HCC patients and 1031 control subjects from nine studies were included in this meta-analysis. The summary estimates for HSPs and AFP are as follows: sensitivity of 0.78 (95% CI: 0.69-0.85) compared to 0.73 (95% CI: 0.65-0.80); specificity of 0.89 (95% CI: 0.81-0.95) compared to 0.86 (95% CI: 0.77-0.91); PLR of 7.4 (95% CI: 3.7-14.9) compared to 5.1 (95% CI: 3.3-8.1); NLR of 0.24 (95% CI: 0.16-0.37) compared to 0.31 (95% CI: 0.24-0.41); DOR of 30.19 (95% CI: 10.68-85.37) compared to 16.34 (95% CI: 9.69-27.56); and AUC of 0.90 (95% CI: 0.87-0.92) compared to 0.85 (95% CI: 0.82-0.88). The pooled sensitivity, specificity, PLR, NLR, DOR and AUC were 0.90 (95% CI: 0.82-0.95), 0.94 (95% CI: 0.82-0.98), 14.5 (95% CI: 4.6-45.4), 0.11 (95% CI: 0.06-0.20), 133.34 (95% CI: 29.65-599.61), and 0.96 (95% CI: 0.94-0.98) for the combination of HSPs and AFP. CONCLUSION Our analysis suggests that HSPs have potential as a biomarker for clinical use in the diagnosis of HCC, and the concurrent utilization of HSPs and AFP shows notable diagnostic effectiveness for HCC.
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Affiliation(s)
- Dan Xiang
- Department of Laboratory Medicine, Ya'an People's Hospital, Yaan, 625000, China
| | - Lifang Fu
- Department of Laboratory Medicine, Ya'an People's Hospital, Yaan, 625000, China
| | - Ying Yang
- Department of Clinical Laboratory, the Second Affiliated Hospital, Army Medical University, Chongqing, 400037, China
| | - ChengJiang Liu
- Department of General Medicine, Affiliated Anqing First People's Hospital of Anhui Medical University, Anqing, 246000, China.
| | - Yong He
- Department of Laboratory Medicine, West China Hospital, Sichuan University, Chengdu, 610041, China.
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3
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Xiang D, Jiang M, Chen Y, Liu C, Li L. Clinicopathological and prognostic significance of heat shock proteins in hepatocellular carcinoma: a systematic review and meta-analysis. Front Oncol 2023; 13:1169979. [PMID: 37601679 PMCID: PMC10436519 DOI: 10.3389/fonc.2023.1169979] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/11/2023] [Accepted: 07/17/2023] [Indexed: 08/22/2023] Open
Abstract
Background Overexpression of heat shock proteins (HSPs) has been observed in a wide range of human tumors, and there is an increasing evidence demonstrated that HSPs play a key role in tumor progression. Several studies were conducted to explore the clinicopathological characteristics and prognostic value of HSPs in hepatocellular carcinoma (HCC), but the results remain controversial. To address this gap, we conducted a systematic review and meta-analysis. Methods The eligible literature was obtained from PubMed, Cochrane library, Web of science, Embase, Chinese National Knowledge Infrastructure and Wan Fang databases. We used the odds ratio (OR) and hazard ratio (HR) as the suitable parameters to assess the clinicopathological features and prognostic value of HSPs in HCC patients. Results The meta-analysis results showed that HSPs expression was associated with overall survival (OS) of HCC patients (HR = 1.61, 95%CI = 1.22-2.13, P=0.001, I 2 = 62.7%). In addition, the pooled results suggested that HSPs expression was significantly correlated with tumor differentiation (OR = 1.33, 95%CI = 1.08-1.65, P = 0.907), vascular invasion (OR = 1.31, 95%CI = 1.02-1.69, P = 0.921) and lymphatic metastasis (OR=1.98, 95%CI= 1.70-2.31, P = 0.740). Meanwhile, the subgroup analysis showed a significant correlation between the expression of HSP27 (HR=1.69, 95%CI = 1.24-2.31, P = 0.674) and HSP90α (HR=2.03, 95%CI = 1.73-2.40, P = 0.743) with OS of HCC patients. Conclusions Our meta-analysis confirms that HSPs expression is closely associated with a worse prognosis in HCC patients, and may be directly involved in tumor differentiation and distant metastasis. In addition, the subgroup analysis results demonstrate that the expression of HSP27 and HSP90α can be served as potential prognostic predictors of HCC.
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Affiliation(s)
- Dan Xiang
- Department of Laboratory Medicine, Ya’an People’s Hospital, Yaan, China
| | - Mengdan Jiang
- Department of Laboratory Medicine, Ya’an People’s Hospital, Yaan, China
| | - Ya Chen
- Department of General Surgery, The First People’s Hospital of Yunnan Province, Kunming, China
| | - Chengjiang Liu
- Department of General Medicine, Affiliated Anqing First People’s Hospital of Anhui Medical University, Anqing, China
| | - Leilei Li
- Disaster Medicine Research Center, West China Hospital, Sichuan University, Chengdu, China
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Mariani A, Tripepi M, Mangoni I, Aseni P. Major Complications in Hepatobiliary and Pancreatic Surgery. THE HIGH-RISK SURGICAL PATIENT 2023:475-490. [DOI: 10.1007/978-3-031-17273-1_44] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
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Prediction of left lobe hypertrophy after right lobe radioembolization of the liver using a clinical data model with external validation. Sci Rep 2022; 12:20718. [PMID: 36456637 PMCID: PMC9715713 DOI: 10.1038/s41598-022-25077-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/08/2021] [Accepted: 11/24/2022] [Indexed: 12/02/2022] Open
Abstract
In cirrhotic patients with hepatocellular carcinoma (HCC), right-sided radioembolization (RE) with Yttrium-90-loaded microspheres is an established palliative therapy and can be considered a "curative intention" treatment when aiming for sequential tumor resection. To become surgical candidate, hypertrophy of the left liver lobe to > 40% (future liver remnant, FLR) is mandatory, which can develop after RE. The amount of radiation-induced shrinkage of the right lobe and compensatory hypertrophy of the left lobe is difficult for clinicians to predict. This study aimed to utilize machine learning to predict left lobe liver hypertrophy in patients with HCC and cirrhosis scheduled for right lobe RE, with external validation. The results revealed that machine learning can accurately predict relative and absolute volume changes of the left liver lobe after right lobe RE. This prediction algorithm could help to estimate the chances of conversion from palliative RE to curative major hepatectomy following significant FLR hypertrophy.
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Shi JY, Sun LY, Quan B, Xing H, Li C, Liang L, Pawlik TM, Zhou YH, Wang H, Gu WM, Chen TH, Lau WY, Shen F, Wang NY, Yang T. A novel online calculator based on noninvasive markers (ALBI and APRI) for predicting post-hepatectomy liver failure in patients with hepatocellular carcinoma. Clin Res Hepatol Gastroenterol 2021; 45:101534. [PMID: 33067168 DOI: 10.1016/j.clinre.2020.09.001] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/20/2020] [Revised: 08/12/2020] [Accepted: 09/01/2020] [Indexed: 02/04/2023]
Abstract
BACKGROUND AND AIM Post-hepatectomy liver failure (PHLF) remains the primary cause of in-hospital mortality after hepatectomy. Identifying predictors of PHLF is important to improve surgical safety. We sought to identify the predictive accuracy of two noninvasive markers, albumin-bilirubin (ALBI) and aspartate aminotransferase to platelet count ratio index (APRI), to predict PHLF among patients with hepatocellular carcinoma (HCC), and to build up an online prediction calculator. METHODS Patients who underwent resection for HCC between 2013 and 2016 at 6 Chinese hospitals were retrospectively analyzed. The independent predictors of PHLF were identified using univariate and multivariate analyses; derivative data were used to construct preoperative and postoperative nomogram models. Receiver operating characteristic (ROC) curves for the two predictive models, and ALBI, APRI, Child-Pugh, model for end-stage liver disease (MELD) scores were compared relative to predictive accuracy for PHLF. RESULTS Among the 767 patients in the analytic cohort, 102 (13.3%) experienced PHLF. Multivariable logistic regression analysis identified high ALBI grade (>-2.6) and high APRI grade (>1.5) as independent risk factors associated with PHLF in both the preoperative and postoperative models. Two nomogram predictive models and corresponding web-based calculators were subsequently constructed. The areas under the ROC curves for the postoperative and preoperative models, APRI, ALBI, MELD and Child-Pugh scores in predicting PHLF were 0.844, 0.789, 0.626, 0.609, 0.569, and 0.560, respectively. CONCLUSIONS ALBI and APRI demonstrated more accurate ability to predict PHLF than Child-Pugh and MELD. Two online calculators that combined ALBI and APRI were proposed as useful preoperative and postoperative tools for individually predicting the occurrence of PHLF among patients with HCC.
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Affiliation(s)
- Jin-Yu Shi
- The Cancer Center, the First Hospital of Jilin University, Changchun, China
| | - Li-Yang Sun
- Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University (Naval Medical University), Shanghai, China; Department of Clinical Medicine, Second Military Medical University (Naval Medical University), Shanghai, China
| | - Bing Quan
- Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University (Naval Medical University), Shanghai, China; Department of Clinical Medicine, Second Military Medical University (Naval Medical University), Shanghai, China
| | - Hao Xing
- Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University (Naval Medical University), Shanghai, China
| | - Chao Li
- Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University (Naval Medical University), Shanghai, China
| | - Lei Liang
- Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University (Naval Medical University), Shanghai, China
| | - Timothy M Pawlik
- Department of Surgery, Ohio State University, Wexner Medical Center, Columbus, OH, United States
| | - Ya-Hao Zhou
- Department of Hepatobiliary Surgery, Pu'er People's Hospital, Yunnan, China
| | - Hong Wang
- Department of General Surgery, Liuyang People's Hospital, Hunan, China
| | - Wei-Min Gu
- The First Department of General Surgery, The Fourth Hospital of Harbin, Heilongjiang, China
| | - Ting-Hao Chen
- Department of General Surgery, Ziyang First People's Hospital, Sichuan, China
| | - Wan Yee Lau
- Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University (Naval Medical University), Shanghai, China; Faculty of Medicine, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, N.T., Hong Kong SAR, China
| | - Feng Shen
- Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University (Naval Medical University), Shanghai, China
| | - Nan-Ya Wang
- The Cancer Center, the First Hospital of Jilin University, Changchun, China.
| | - Tian Yang
- Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University (Naval Medical University), Shanghai, China.
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Jin H, Wang H, Li G, Hou Q, Wu W, Liu F. Risk factors for early postoperative recurrence in single and small hepatitis B virus-associated primary hepatocellular carcinoma. J Int Med Res 2021; 48:300060520961260. [PMID: 33044114 PMCID: PMC7556173 DOI: 10.1177/0300060520961260] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022] Open
Abstract
Objective To investigate the risk factors of early postoperative recurrence in patients with single and small (≤3 cm) hepatitis B virus-associated primary hepatocellular carcinoma (HBV-HCC). Methods This retrospective study analyzed patients with single and small HBV-HCC. All patients were followed up for 1 year after surgery. Results Among 182 patients, 54 patients had early recurrence within 1 year. The recurrence group had higher proportions of men, drinking history, Child–Turcotte–Pugh (CTP) class C, patients who underwent transarterial chemoembolization (TACE), and serum alpha-fetoprotein (AFP) >10 ng/mL as well as higher gamma-glutamyl transpeptidase (GGT) levels and lower total protein (TP) and CD8+ T lymphocyte levels than the no recurrence group. Cox multivariate regression analysis demonstrated that drinking history (HR, 1.312; 95% CI, 1.042–1.652), CTP class C (HR, 1.236; 95% CI, 1.037–1.473), TACE treatment (HR, 1.241; 95% CI, 1.026–1.501), GGT (HR, 1.138; 95% CI, 1.042–1.243), TP (HR, 0.729; 95% CI, 0.555–0.957), and AFP (HR, 2.519; 95% CI, 1.343–4.726) were independently associated with early postoperative recurrence. Conclusion Drinking history, CTP class C, TACE, serum AFP, GGT, and TP levels were independently associated with early postoperative recurrence in patients with single and small HBV-HCC.
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Affiliation(s)
- Hongmei Jin
- Department of Hepatology, Qingdao No. 6 People's Hospital, Qingdao, Shandong, China
| | - Hui Wang
- Department of Hepatology, Qingdao No. 6 People's Hospital, Qingdao, Shandong, China
| | - Guanghao Li
- Department of Hepatobiliary surgery, Qingdao No. 6 People's Hospital, Qingdao, Shandong, China
| | - Qingshun Hou
- Department of Hepatology, Qingdao No. 6 People's Hospital, Qingdao, Shandong, China
| | - Wei Wu
- Department of Hepatology, Qingdao No. 6 People's Hospital, Qingdao, Shandong, China
| | - Fuhui Liu
- Department of Hepatology, Qingdao No. 6 People's Hospital, Qingdao, Shandong, China
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Li JD, Diao YK, Li J, Wu H, Sun LY, Gu WM, Wang H, Chen TH, Zeng YY, Zhou YH, Wang Y, Zhang YM, Liang YJ, Lau WY, Li C, Liang L, Wang MD, Zhang CW, Shen F, Shao CH, Yang T. Association between preoperative prealbumin level and postoperative mortality and morbidity after hepatic resection for hepatocellular carcinoma: A multicenter study from a HBV-endemic area. Am J Surg 2021; 221:1024-1032. [PMID: 32951853 DOI: 10.1016/j.amjsurg.2020.08.036] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/09/2020] [Revised: 07/24/2020] [Accepted: 08/26/2020] [Indexed: 02/07/2023]
Abstract
BACKGROUND Prealbumin is a more sensitive serum biomarker in reflecting liver function and nutritional status than albumin, because of its shorter half-life and its characteristics that could hardly be affected by supplemental venous infusion of albumin or blood transfusion. This study aimed to identify whether preoperative prealbumin level was associated with postoperative mortality and morbidity after hepatic resection for patients with hepatocellular carcinoma (HCC). METHODS From a Chinese multicenter database, patients who underwent hepatic resection for HCC were divided into the low and normal prealbumin groups by using 17 mg/dL as the cut-off level for serum prealbumin taken within a week before surgery. Using univariable and multivariable logistic regression analyses, independent predictors associated with postoperative 30-day and 90-day mortality, 30-day overall and major morbidity, and postoperative hepatic insufficiency were identified. RESULTS Among 1356 patients, 409 (30.2%) had a low preoperative prealbumin level. Postoperative 30-day and 90-day mortality, and 30-day overall and major morbidity in the low prealbumin group were significantly higher than the normal prealbumin group (2.9% vs. 0.5%, 5.1% vs. 1.5%, 35.7% vs. 18.4%, and 14.4% vs. 6.5%, respectively, all P < 0.001). Multivariable analyses identified that preoperative prealbumin level, but not albumin level, was independently associated with postoperative 30-day mortality (OR: 3.486, 95% CI: 1.184-10.265), 90-day mortality (2.504, 1.219-5.145), 30-day overall morbidity (1.727, 1.302-2.292), 30-day major morbidity (1.770, 1.155-2.711) and postoperative hepatic insufficiency (1.967, 1.119-3.427). CONCLUSIONS Preoperative prealbumin level could be used to predict postoperative morbidity and mortality for patients treated with hepatic resection for HCC.
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Affiliation(s)
- Ju-Dong Li
- Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University (Naval Medical University), Shanghai, China; Department of General Surgery, Changzheng Hospital, Second Military Medical University (Naval Medical University), Shanghai, China
| | - Yong-Kang Diao
- Department of Hepatobiliary, Pancreatic and Minimal Invasive Surgery, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Zhejiang, China
| | - Jie Li
- Department of Hepatobiliary Surgery, Fuyang People's Hospital, Anhui, China
| | - Han Wu
- Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University (Naval Medical University), Shanghai, China
| | - Li-Yang Sun
- Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University (Naval Medical University), Shanghai, China
| | - Wei-Min Gu
- The First Department of General Surgery, The Fourth Hospital of Harbin, Heilongjiang, China
| | - Hong Wang
- Department of General Surgery, Liuyang People's Hospital, Hunan, China
| | - Ting-Hao Chen
- Department of General Surgery, Ziyang First People's Hospital, Sichuan, China
| | - Yong-Yi Zeng
- Department of Hepatobiliary Surgery, Mengchao Hepatobiliary Hospital, Fujian Medical University, Fujian, China
| | - Ya-Hao Zhou
- Department of Hepatobiliary Surgery, Pu'er People's Hospital, Yunnan, China
| | - Yu Wang
- Department of Hepatobiliary Surgery, Chongqing University Cancer Hospital, Chongqing, China
| | - Yao-Ming Zhang
- The 2nd Department of Hepatobiliary Surgery, Meizhou People's Hospital, Guangdong, China
| | - Ying-Jian Liang
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Harbin Medical University, Heilongjiang, China
| | - Wan Yee Lau
- Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University (Naval Medical University), Shanghai, China; Faculty of Medicine, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong, China
| | - Chao Li
- Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University (Naval Medical University), Shanghai, China
| | - Lei Liang
- Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University (Naval Medical University), Shanghai, China
| | - Ming-Da Wang
- Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University (Naval Medical University), Shanghai, China
| | - Cheng-Wu Zhang
- Department of Hepatobiliary, Pancreatic and Minimal Invasive Surgery, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Zhejiang, China
| | - Feng Shen
- Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University (Naval Medical University), Shanghai, China
| | - Cheng-Hao Shao
- Department of General Surgery, Changzheng Hospital, Second Military Medical University (Naval Medical University), Shanghai, China.
| | - Tian Yang
- Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University (Naval Medical University), Shanghai, China.
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Shehta A, Lee JM, Suh KS, Kim HC, Hong SK, Cho JH, Yi NJ, Lee KW. Bridging and downstaging role of trans-arterial radio-embolization for expected small remnant volume before liver resection for hepatocellular carcinoma. Ann Hepatobiliary Pancreat Surg 2020; 24:421-430. [PMID: 33234744 PMCID: PMC7691198 DOI: 10.14701/ahbps.2020.24.4.421] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/23/2020] [Revised: 07/13/2020] [Accepted: 07/13/2020] [Indexed: 02/06/2023] Open
Abstract
Backgrounds/Aims To evaluate our initial experience of bridging role of trans-arterial radio-embolization (TARE) before major hepatectomy for hepatocellular carcinoma (HCC) in risky patients with small expected remnant liver volume (ERLV). Methods We reviewed the data of patients with HCC who underwent major hepatectomy after TARE during the period between March and December 2017. Patients included had uni-lobar large HCC (>5 cm) requiring major hepatectomy with small ERLV. Results Five patients were included in our study. All patients were Child Pugh class A. A single session of TARE was applied in all patients. None developed any adverse events related to irradiation. The mean tumor size at baseline was 8.4 cm and 6.1 cm after TARE (p=0.077). The mean % of tumor shrinkage was 24.5%. ERLV improved from 354.6 ml at baseline to 500.8 ml after TARE (p=0.012). ERLV percentage improved from 27.2% at baseline to 38.1% after TARE (p=0.004). The mean % of ERLV was 39.5%. The mean interval time between TARE and resection was 99.6 days. Four patients (80%) underwent right hemi-hepatectomy and one patient (20%) underwent extended right hemi-hepatectomy. The mean operation time was 151 minutes, and mean blood loss was 56 ml. The mean hospital stay was 13.8 days, and one patient (20%) developed postoperative morbidity. After a mean follow-up of 15 months, all patients were alive with no recurrence. Conclusions Yttrium-90 TARE can play a bridging role before major hepatectomy for borderline resectable HCC in risky patients with small ERLV.
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Affiliation(s)
- Ahmed Shehta
- Department of Surgery, Seoul National University College of Medicine, Seoul, Korea.,Liver Transplantation Unit, Gastrointestinal Surgery Center, College of Medicine, Mansoura University, Mansoura, Egypt
| | - Jeong-Moo Lee
- Department of Surgery, Seoul National University College of Medicine, Seoul, Korea
| | - Kyung-Suk Suh
- Department of Surgery, Seoul National University College of Medicine, Seoul, Korea
| | - Hyo-Cheol Kim
- Department of Radiology, Seoul National University Hospital, Seoul, Korea
| | - Suk Kyun Hong
- Department of Surgery, Seoul National University College of Medicine, Seoul, Korea
| | - Jae-Hyung Cho
- Department of Surgery, Seoul National University College of Medicine, Seoul, Korea
| | - Nam-Joon Yi
- Department of Surgery, Seoul National University College of Medicine, Seoul, Korea
| | - Kwang-Woong Lee
- Department of Surgery, Seoul National University College of Medicine, Seoul, Korea
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10
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De Raffele E, Mirarchi M, Cuicchi D, Lecce F, Casadei R, Ricci C, Selva S, Minni F. Simultaneous colorectal and parenchymal-sparing liver resection for advanced colorectal carcinoma with synchronous liver metastases: Between conventional and mini-invasive approaches. World J Gastroenterol 2020; 26:6529-6555. [PMID: 33268945 PMCID: PMC7673966 DOI: 10.3748/wjg.v26.i42.6529] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/12/2020] [Revised: 10/05/2020] [Accepted: 10/26/2020] [Indexed: 02/06/2023] Open
Abstract
The optimal timing of surgery in case of synchronous presentation of colorectal cancer and liver metastases is still under debate. Staged approach, with initial colorectal resection followed by liver resection (LR), or even the reverse, liver-first approach in specific situations, is traditionally preferred. Simultaneous resections, however, represent an appealing strategy, because may have perioperative risks comparable to staged resections in appropriately selected patients, while avoiding a second surgical procedure. In patients with larger or multiple synchronous presentation of colorectal cancer and liver metastases, simultaneous major hepatectomies may determine worse perioperative outcomes, so that parenchymal-sparing LR should represent the most appropriate option whenever feasible. Mini-invasive colorectal surgery has experienced rapid spread in the last decades, while laparoscopic LR has progressed much slower, and is usually reserved for limited tumours in favourable locations. Moreover, mini-invasive parenchymal-sparing LR is more complex, especially for larger or multiple tumours in difficult locations. It remains to be established if simultaneous resections are presently feasible with mini-invasive approaches or if we need further technological advances and surgical expertise, at least for more complex procedures. This review aims to critically analyze the current status and future perspectives of simultaneous resections, and the present role of the available mini-invasive techniques.
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Affiliation(s)
- Emilio De Raffele
- Division of Pancreatic Surgery, Department of Digestive Diseases, Azienda Ospedaliero-Universitaria di Bologna, Policlinico S.Orsola-Malpighi, 40138 Bologna, Italy
| | - Mariateresa Mirarchi
- Dipartimento Strutturale Chirurgico, Ospedale SS Antonio e Margherita, 15057 Tortona (AL), Italy
| | - Dajana Cuicchi
- Surgery of the Alimentary Tract, Department of Digestive Diseases, Azienda Ospedaliero-Universitaria di Bologna, Policlinico S.Orsola-Malpighi, 40138 Bologna, Italy
| | - Ferdinando Lecce
- Surgery of the Alimentary Tract, Department of Digestive Diseases, Azienda Ospedaliero-Universitaria di Bologna, Policlinico S.Orsola-Malpighi, 40138 Bologna, Italy
| | - Riccardo Casadei
- Division of Pancreatic Surgery, Department of Medical and Surgical Sciences (DIMEC), Alma Mater Studiorum, University of Bologna, 40138 Bologna, Italy
| | - Claudio Ricci
- Division of Pancreatic Surgery, Department of Medical and Surgical Sciences (DIMEC), Alma Mater Studiorum, University of Bologna, 40138 Bologna, Italy
| | - Saverio Selva
- Division of Pancreatic Surgery, Department of Digestive Diseases, Azienda Ospedaliero-Universitaria di Bologna, Policlinico S.Orsola-Malpighi, 40138 Bologna, Italy
| | - Francesco Minni
- Division of Pancreatic Surgery, Department of Medical and Surgical Sciences (DIMEC), Alma Mater Studiorum, University of Bologna, 40138 Bologna, Italy
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11
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Wu Z, Chen W, Ouyang T, Liu H, Cao L. Management and survival for patients with stage-I hepatocellular carcinoma: An observational study based on SEER database. Medicine (Baltimore) 2020; 99:e22118. [PMID: 33031259 PMCID: PMC7544265 DOI: 10.1097/md.0000000000022118] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
It is controversial regarding the treatment allocation for patients with stage I hepatocellular carcinoma (SI-HCC). The aim of the present study was to compare the long-term survival in SI-HCC patients undergoing liver transplantation (LT), liver resection (LR), local tumor destruction (LTD), or none. SI-HCC patients diagnosed between 2004 and 2015 were extracted from the SEER 18 registry database. Multivariable Cox models and propensity score matching (PSM) method were used to explore the association between surgical methods and long-term prognosis. A total of 5165 patients with stage I (AJCC, 6th or 7th) HCC were included in the study. Only 36.9% of patients diagnosed with HCC in stage I received surgical therapy. The incidence of LT was decreased over time (P < .001). In the multivariable-adjusted cohort (n = 5165), after adjusting potential confounding factors, a clear prognostic advantage of LT was observed in OS (P < .0001) compared with patients after LR. Patients undergoing LTD had a worse OS in comparison with patients who underwent LR (P < .0001). Patients who received no surgical treatment had the worst OS (P < .0001) among 4 treatment groups. In stratified analyses, the salutary effects of LT vs LR on OS were consistent across all subgroups except for a similar result in the noncirrhotic subgroup (P = .4414). The inferior survival effects of LTD vs LR on OS were consistent across all subgroups, and even in the subgroup with tumor size < 3 cm (P = .0342). In the PSM cohort, patients in LT group showed a better OS (P < .001) than patients in LR group (P < .0001) and patients undergoing LTD had a worse OS compared with patients who underwent LR (P = .00059). In conclusion, LT offered a survival advantage compared with LR among patients with Stage I HCC. LT is the best surgical treatment for stage I HCC in patients with advanced fibrosis, whereas LR provides comparable long-term outcomes to LT in patients without advanced fibrosis and should be considered as the first-line surgical option. LTD can be used as an alternative method when LR and LT are unavailable.
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Affiliation(s)
| | | | | | | | - Lingling Cao
- Department of Endocrinology, Jiujiang NO.1 People's Hospital, Jiujiang, Jiangxi Province, China
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12
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Patel K, Lamm R, Altshuler P, Dang H, Shah AP. Hepatocellular Carcinoma-The Influence of Immunoanatomy and the Role of Immunotherapy. Int J Mol Sci 2020; 21:ijms21186757. [PMID: 32942580 PMCID: PMC7555667 DOI: 10.3390/ijms21186757] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/28/2020] [Revised: 09/09/2020] [Accepted: 09/14/2020] [Indexed: 02/07/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is a leading cause of cancer-related morbidity and mortality worldwide. Most patients are diagnosed with advanced disease, limiting their options for treatment. While current treatments are adequate for lower staged disease, available systemic treatments are limited, with marginal benefit at best. Chimeric antigen receptor (CAR) T cell therapy, effective in treating liquid tumors such as B-cell lymphoma, presents a potentially promising treatment option for advanced HCC. However, new challenges specific to solid tumors, such as tumor immunoanatomy or the immune cell presence and position anatomically and the tumor microenvironment, need to be defined and overcome. Immunotherapy currently in use must be re-engineered and re-envisioned to treat HCC with the hopes of ushering in an answer to advanced stage solid tumor disease processes. Future therapy options must address the uniqueness of the tumors under the umbrella of HCC. This review strives to summarize HCC, its staging system, current therapy and immunotherapy medications currently being utilized or studied in the treatment of HCC with the hopes of highlighting what is being done and suggesting what needs to be done in the future to champion this therapy as an effective option.
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Affiliation(s)
- Keyur Patel
- Department of Surgery, Thomas Jefferson University, Philadelphia, PA 19144, USA; (K.P.); (R.L.); (P.A.)
| | - Ryan Lamm
- Department of Surgery, Thomas Jefferson University, Philadelphia, PA 19144, USA; (K.P.); (R.L.); (P.A.)
| | - Peter Altshuler
- Department of Surgery, Thomas Jefferson University, Philadelphia, PA 19144, USA; (K.P.); (R.L.); (P.A.)
| | - Hien Dang
- Department of Surgery, Thomas Jefferson University, Philadelphia, PA 19144, USA; (K.P.); (R.L.); (P.A.)
- Sidney Kimmel Cancer Center, Philadelphia, PA 19107, USA
- Correspondence: (H.D.); (A.P.S.)
| | - Ashesh P. Shah
- Department of Surgery, Thomas Jefferson University, Philadelphia, PA 19144, USA; (K.P.); (R.L.); (P.A.)
- Correspondence: (H.D.); (A.P.S.)
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13
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Takahashi K, Liang C, Oda T, Ohkohchi N. Platelet and liver regeneration after liver surgery. Surg Today 2020; 50:974-983. [PMID: 31720801 DOI: 10.1007/s00595-019-01890-x] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/18/2019] [Accepted: 08/03/2019] [Indexed: 02/06/2023]
Abstract
The success of liver surgery, including resection and transplantation, is largely dependent on the ability of the liver to regenerate. Despite substantial improvement in surgical techniques and perioperative care, one of the main concerns is post-hepatectomy liver failure and early allograft dysfunction, both of which are associated with impaired liver regeneration. Recent studies have demonstrated the positive role of platelets in promoting liver regeneration and protecting hepatocytes; however, the underlying mechanisms responsible for these effects are not fully understood. In this review, we updated the accumulated evidence of the role of platelets in promoting liver regeneration, with a focus on liver resection and liver transplantation. The goal of these studies was to support the clinical implementation of platelet agents, such as thrombopoietin receptor agonists, to augment liver regeneration after liver surgery. This "platelet therapy" may become a treatment choice for post-hepatectomy liver failure and early allograft dysfunction.
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Affiliation(s)
- Kazuhiro Takahashi
- Department of Surgery, University of Tsukuba, 1-1-1, Tennoudai, Tsukuba, Ibaraki, 305-8575, Japan
- Department of Surgery, Mito Central Hospital, 1136-1, Rokutanda-cho, Mito, 311-1135, Japan
| | - Chen Liang
- Department of Surgery, University of Tsukuba, 1-1-1, Tennoudai, Tsukuba, Ibaraki, 305-8575, Japan
- Department of Surgery, Mito Central Hospital, 1136-1, Rokutanda-cho, Mito, 311-1135, Japan
| | - Tatsuya Oda
- Department of Surgery, University of Tsukuba, 1-1-1, Tennoudai, Tsukuba, Ibaraki, 305-8575, Japan
- Department of Surgery, Mito Central Hospital, 1136-1, Rokutanda-cho, Mito, 311-1135, Japan
| | - Nobuhiro Ohkohchi
- Department of Surgery, University of Tsukuba, 1-1-1, Tennoudai, Tsukuba, Ibaraki, 305-8575, Japan.
- Department of Surgery, Mito Central Hospital, 1136-1, Rokutanda-cho, Mito, 311-1135, Japan.
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14
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Nomura A, Ishigami M, Honda T, Kuzuya T, Ishizu Y, Ito T, Kamei H, Onishi Y, Ogura Y, Fujishiro M. Limitation of non-transplant treatment and proper timing for liver transplantation in patients with hepatocellular carcinoma considering long-term survival. Medicine (Baltimore) 2020; 99:e21161. [PMID: 32664152 PMCID: PMC7360274 DOI: 10.1097/md.0000000000021161] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/24/2022] Open
Abstract
In this study, we investigated the long-term survival of patients with hepatocellular carcinoma (HCC) after conventional treatment other than liver transplantation (LT) in our institute and discuss the limitation of non-transplant treatment for HCC and the proper indictors of LT in the recent comprehensive era.Between 2003 and 2016, 181 patients with HCC aged ≦70 years received active treatment including liver resection, radiofrequency ablation (RFA), and transcatheter arterial chemoembolization (TACE). We analyzed the factors associated with overall survival and proposed new priority for the indicators of LT in HCC patients according to the extracted factors by comparing the survival with 39 transplanted patients with HCC.Child-Turcotte-Pugh (CTP) score (HR: 1.276; 95% CI: 1.049-1.552, P = .015), and number of tumors (HR: 1.238; 95% CI: 1.112-1.377, P < .001) were selected as significant factors associated with the survival after active treatments for HCC. Patients with LT had significantly better long-term survival compared with those with non-transplant patients regardless of aforementioned factors. However, regarding relatively short survival (3 years), patients with CTP score of ≧9 and/or ≧3 tumors with non-transplant treatment had poorer survival compared with those of transplanted patients (P < .05).We propose that CTP score of 9 and/or 3 tumors before non-transplant, intensive treatment might be a new priority for considering indicators of LT in patients with HCC.
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Affiliation(s)
- Aya Nomura
- Department of Gastroenterology and Hepatology
| | | | | | | | - Yoji Ishizu
- Department of Gastroenterology and Hepatology
| | | | - Hideya Kamei
- Department of Transplant Surgery, Nagoya University School of Medicine, Nagoya, Japan
| | - Yasuharu Onishi
- Department of Transplant Surgery, Nagoya University School of Medicine, Nagoya, Japan
| | - Yasuhiro Ogura
- Department of Transplant Surgery, Nagoya University School of Medicine, Nagoya, Japan
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15
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Hobeika C, Cauchy F, Sartoris R, Beaufrère A, Yoh T, Vilgrain V, Rautou PE, Paradis V, Bouattour M, Ronot M, Soubrane O. Relevance of liver surface nodularity for preoperative risk assessment in patients with resectable hepatocellular carcinoma. Br J Surg 2020; 107:878-888. [PMID: 32118298 DOI: 10.1002/bjs.11511] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2019] [Revised: 12/08/2019] [Accepted: 12/14/2019] [Indexed: 02/06/2023]
Abstract
BACKGROUND Quantification of liver surface nodularity (LSN) on routine preoperative CT images allows detection of cirrhosis and clinically significant portal hypertension. This study aimed to assess the relevance of LSN in preoperative assessment of operative risks for patients with resectable hepatocellular carcinoma (HCC). METHODS All patients undergoing hepatectomy for HCC between 2012 and 2017 were analysed retrospectively. LSN was assessed at the liver-fat interface on the left liver lobe on preoperative CT images. The feasibility of LSN quantification was assessed. The association between LSN and outcomes (severe complications and posthepatectomy liver failure (PHLF)) was evaluated by multivariable analysis and after propensity score matching. RESULTS Among 210 patients, LSN measurement was successful in 187 (89·0 per cent). Among these, the median LSN score was 2·42 (i.q.r. 2·21-2·66) and 52·9 per cent had severe fibrosis, including 33·7 per cent with cirrhosis. LSN score increased with hepatic venous pressure gradient (P = 0·048), severity of steatosis (P = 0·011) and fibrosis grade (P = 0·001). LSN score was independently associated with severe complications (odds ratio (OR) 5·25; P = 0·006) and PHLF (OR 6·78; P = 0·003). After matching with respect to model for end-stage liver disease, aspartate aminotransferase-to-platelet ratio index and fibrosis-4 score, patients with a LSN score of 2·63 or higher retained an increased risk of PHLF (OR 5·81; P = 0·018). In the subgroup of patients without severe fibrosis, LSN was accurate in predicting severe complications (P = 0·005). Patients with (P = 0·039) or without (P = 0·018) severe fibrosis with increased LSN score had a higher comprehensive complication index score. Among patients with cirrhosis who had clinically significant portal hypertension, a LSN value below 2·63 ruled out the risk of PHLF. CONCLUSION LSN measurement represents a practical tool that may allow improvement in the preoperative evaluation and management of patients with HCC.
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Affiliation(s)
- C Hobeika
- Department of Hepatopancreatobiliary Surgery and Liver Transplantation, Beaujon Hospital, Assistance Publique Hôpitaux de Paris and Université de Paris, Clichy, France
| | - F Cauchy
- Department of Hepatopancreatobiliary Surgery and Liver Transplantation, Beaujon Hospital, Assistance Publique Hôpitaux de Paris and Université de Paris, Clichy, France
| | - R Sartoris
- Department of Radiology, Beaujon Hospital, Assistance Publique Hôpitaux de Paris and Université de Paris, Clichy, France
| | - A Beaufrère
- Department of Pathology, Beaujon Hospital, Assistance Publique Hôpitaux de Paris and Université de Paris, Clichy, France
| | - T Yoh
- Department of Hepatopancreatobiliary Surgery and Liver Transplantation, Beaujon Hospital, Assistance Publique Hôpitaux de Paris and Université de Paris, Clichy, France
| | - V Vilgrain
- Department of Radiology, Beaujon Hospital, Assistance Publique Hôpitaux de Paris and Université de Paris, Clichy, France
| | - P E Rautou
- Department of Hepatology, Beaujon Hospital, Assistance Publique Hôpitaux de Paris and Université de Paris, Clichy, France
| | - V Paradis
- Department of Pathology, Beaujon Hospital, Assistance Publique Hôpitaux de Paris and Université de Paris, Clichy, France
| | - M Bouattour
- Department of Hepatology, Beaujon Hospital, Assistance Publique Hôpitaux de Paris and Université de Paris, Clichy, France
| | - M Ronot
- Department of Radiology, Beaujon Hospital, Assistance Publique Hôpitaux de Paris and Université de Paris, Clichy, France
| | - O Soubrane
- Department of Hepatopancreatobiliary Surgery and Liver Transplantation, Beaujon Hospital, Assistance Publique Hôpitaux de Paris and Université de Paris, Clichy, France
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16
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Zhang J, Tang N, Zhao Y, Zhao R, Fu X, Zhao D, Zhao Y, Huang L, Li C, Qiu Y, Xue B, Fang L. Global Phosphoproteomic Analysis Reveals Significant Metabolic Reprogramming in the Termination of Liver Regeneration in Mice. J Proteome Res 2020; 19:1788-1799. [PMID: 32105074 PMCID: PMC7205775 DOI: 10.1021/acs.jproteome.0c00028] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Phosphorylation is crucial in regulating various biological processes. However, comprehensive phosphoproteomic profiling in the termination of liver regeneration (LR) is still missing. Here, we used Tandem Mass Tag (TMT) labeling coupled with phosphopeptide enrichment and two-dimensional (2D) liquid chromatography-mass spectrometry (LC-MS)/MS analysis to establish a global phosphoproteomic map in the liver of mice at day 5 after partial hepatectomy (PH). Altogether, 9731 phosphosites from 3443 proteins were identified and 7802 phosphosites from 2980 proteins were quantified. Motif analysis of the identified phosphosites revealed a diverse array of consensus sequences, suggesting that multiple kinase families including ERK/MAPK, PKA/PKC, CaMK-II, CKII, and CDK may be involved in the termination of LR. Functional clustering analysis of proteins with dysregulated phosphosites showed that they mainly participate in metabolic pathways, DNA replication, and tight junction. More importantly, the deletion of PP2Acα in the liver remarkably changes the overall phosphorylation profile, indicating its critical role in regulating the termination of LR. Finally, several differentially phosphorylated sites were validated by co-immunoprecipitation and Western blot. Taken together, our data unravel the first comprehensive phosphoproteomic map in the termination of LR in mice, which greatly expands our knowledge in the complicated regulation of this process and provides new directions for the treatment of liver cancer using liver resection.
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Affiliation(s)
- Jingzi Zhang
- Model Animal Research Center and Medical School of Nanjing University, Nanjing 210093, China
| | - Neng Tang
- Nanjing Drum Tower Hospital, Medical School of Nanjing University, Nanjing 210093, China
| | - Yinjuan Zhao
- Collaborative Innovation Center of Sustainable Forestry in Southern China, College of Forestry, Nanjing Forestry University, Nanjing 210037, China
| | - Ruoyu Zhao
- Model Animal Research Center and Medical School of Nanjing University, Nanjing 210093, China
| | - Xiao Fu
- Nanjing Drum Tower Hospital, Medical School of Nanjing University, Nanjing 210093, China
| | - Dandan Zhao
- Model Animal Research Center and Medical School of Nanjing University, Nanjing 210093, China
| | - Yue Zhao
- Model Animal Research Center and Medical School of Nanjing University, Nanjing 210093, China
| | - Lan Huang
- Department of Physiology and Biophysics, University of California, Irvine, CA 92697, USA
| | - Chaojun Li
- Model Animal Research Center and Medical School of Nanjing University, Nanjing 210093, China
| | - Yudong Qiu
- Nanjing Drum Tower Hospital, Medical School of Nanjing University, Nanjing 210093, China
| | - Bin Xue
- Core Laboratory, Sir Run Run Hospital, Nanjing Medical University, Nanjing, 211166, China
| | - Lei Fang
- Model Animal Research Center and Medical School of Nanjing University, Nanjing 210093, China
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17
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Kyuno D, Qian B, Groß W, Schäfer M, Ryschich E. Endothelium capture-based liver segment imaging using vascular endothelial growth factor receptor 2 in preclinical ex vivo models. BJS Open 2020; 4:332-341. [PMID: 31965760 PMCID: PMC7093791 DOI: 10.1002/bjs5.50253] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/18/2019] [Revised: 11/08/2019] [Accepted: 11/20/2019] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Near-infrared (NIR) imaging of liver segments provides substantial information for surgeons performing liver resection. It was hypothesized that ramucirumab, an endothelium-specific antibody approved by the Food and Drug Administration, could be used for liver segment imaging using the endothelium capture principle. METHODS The capture efficacy of anti-vascular endothelial growth factor receptor (VEGFR) 2 monoclonal antibodies (mAbs) and segment imaging were studied in a mouse model. Binding of ramucirumab in human and porcine tissues was studied using immunofluorescence staining. Isolated porcine liver perfusion was used to analyse the labelling and NIR imaging of selected liver segments. RESULTS VEGFR2 is well expressed on the endothelium of the smallest microvascular blood vessels in mouse, porcine and human liver tissues, as well as in human liver tumours. Perfusion of selected segments in the isolated liver model showed high capture of the anti-VEGFR2 (clone 522302) mAb and ramucirumab in mice and pigs respectively. NIR imaging of selected segments was achieved using isolated porcine liver perfusion with IRDye® 800CW-conjugated ramucirumab. CONCLUSION VEGFR2 is well expressed on the smallest microvascular blood vessels and can capture antibodies during single intravascular passages with high efficacy. The ex vivo imaging of a selected segment using endothelial capture of ramucirumab demonstrates the potential of this antibody for intraoperative navigation in liver surgery. Surgical relevance Imaging of liver segments provides substantial information for surgeons when performing liver resection. The antivascular endothelial growth factor receptor (VEGFR) 2 antibody ramucirumab conjugated with near-infrared dye could visualize selected liver segments using an endothelial capture-based approach in an isolated perfusion liver model. The ex vivo imaging of a selected segment using endothelial capture of ramucirumab demonstrates the potential of this anti-VEGFR2 antibody for intraoperative navigation in liver surgery.
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Affiliation(s)
- D. Kyuno
- Department of General, Visceral and Transplantation SurgeryUniversity Hospital HeidelbergHeidelbergGermany
- Department of Surgery, Surgical Oncology and ScienceSapporo Medical UniversitySapporoJapan
| | - B. Qian
- Department of General, Visceral and Transplantation SurgeryUniversity Hospital HeidelbergHeidelbergGermany
| | - W. Groß
- Department of General, Visceral and Transplantation SurgeryUniversity Hospital HeidelbergHeidelbergGermany
| | - M. Schäfer
- Department of General, Visceral and Transplantation SurgeryUniversity Hospital HeidelbergHeidelbergGermany
| | - E. Ryschich
- Department of General, Visceral and Transplantation SurgeryUniversity Hospital HeidelbergHeidelbergGermany
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18
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Chagas AL, Mattos AAD, Carrilho FJ, Bittencourt PL, Vezozzo DCP, Horvat N, Rocha MDS, Alves VAF, Coral GP, Alvares-DA-Silva MR, Barros FMDR, Menezes MR, Monsignore LM, Coelho FF, Silva RFD, Silva RDCMA, Boin IDFSF, D Albuquerque LAC, Garcia JHP, Felga GEG, Moreira AM, Braghiroli MIFM, Hoff PMG, Mello VBD, Dottori MF, Branco TP, Schiavon LDL, Costa TDFA. BRAZILIAN SOCIETY OF HEPATOLOGY UPDATED RECOMMENDATIONS FOR DIAGNOSIS AND TREATMENT OF HEPATOCELLULAR CARCINOMA. ARQUIVOS DE GASTROENTEROLOGIA 2020; 57:1-20. [PMID: 32294682 DOI: 10.1590/s0004-2803.202000000-20] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/13/2019] [Accepted: 12/19/2019] [Indexed: 02/06/2023]
Abstract
Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related mortality worldwide. The Brazilian Society of Hepatology (SBH) published in 2015 its first recommendations about the management of HCC. Since then, new data have emerged in the literature, prompting the governing board of SBH to sponsor a single-topic meeting in August 2018 in São Paulo. All the invited experts were asked to make a systematic review of the literature reviewing the management of HCC in subjects with cirrhosis. After the meeting, all panelists gathered together for the discussion of the topics and the elaboration of updated recommendations. The text was subsequently submitted for suggestions and approval of all members of the Brazilian Society of Hepatology through its homepage. The present manuscript is the final version of the reviewed manuscript containing the recommendations of SBH.
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Affiliation(s)
- Aline Lopes Chagas
- Universidade de São Paulo, Faculdade de Medicina, Hospital das Clínicas, São Paulo, SP, Brasil
- Universidade de São Paulo, Instituto do Câncer do Estado de São Paulo, São Paulo, SP, Brasil
| | - Angelo Alves de Mattos
- Universidade Federal de Ciências da Saúde de Porto Alegre e Irmandade da Santa Casa de Misericórdia de Porto Alegre, Porto Alegre, RS, Brasil
| | - Flair José Carrilho
- Universidade de São Paulo, Faculdade de Medicina, Hospital das Clínicas, São Paulo, SP, Brasil
- Universidade de São Paulo, Instituto do Câncer do Estado de São Paulo, São Paulo, SP, Brasil
| | | | | | - Natally Horvat
- Universidade de São Paulo, Faculdade de Medicina, Hospital das Clínicas, São Paulo, SP, Brasil
- Hospital Sírio-Libanês, São Paulo, SP, Brasil
| | - Manoel de Souza Rocha
- Universidade de São Paulo, Faculdade de Medicina, Hospital das Clínicas, São Paulo, SP, Brasil
| | - Venâncio Avancini Ferreira Alves
- Universidade de São Paulo, Faculdade de Medicina, Hospital das Clínicas, São Paulo, SP, Brasil
- Universidade de São Paulo, Instituto do Câncer do Estado de São Paulo, São Paulo, SP, Brasil
| | - Gabriela Perdomo Coral
- Universidade Federal de Ciências da Saúde de Porto Alegre e Irmandade da Santa Casa de Misericórdia de Porto Alegre, Porto Alegre, RS, Brasil
| | | | | | - Marcos Roberto Menezes
- Universidade de São Paulo, Faculdade de Medicina, Hospital das Clínicas, São Paulo, SP, Brasil
- Universidade de São Paulo, Instituto do Câncer do Estado de São Paulo, São Paulo, SP, Brasil
- Hospital Sírio-Libanês, São Paulo, SP, Brasil
| | - Lucas Moretti Monsignore
- Universidade de São Paulo, Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto, São Paulo, SP, Brasil
| | | | - Renato Ferreira da Silva
- Faculdade de Medicina de São José do Rio Preto (FAMERP) e Hospital de Base de São José do Rio Preto (FUNFARME), São José do Rio Preto, SP, Brasil
| | - Rita de Cássia Martins Alves Silva
- Faculdade de Medicina de São José do Rio Preto (FAMERP) e Hospital de Base de São José do Rio Preto (FUNFARME), São José do Rio Preto, SP, Brasil
| | | | | | | | | | - Airton Mota Moreira
- Universidade de São Paulo, Faculdade de Medicina, Hospital das Clínicas, São Paulo, SP, Brasil
- Universidade de São Paulo, Instituto do Câncer do Estado de São Paulo, São Paulo, SP, Brasil
| | | | - Paulo Marcelo Gehm Hoff
- Universidade de São Paulo, Instituto do Câncer do Estado de São Paulo, São Paulo, SP, Brasil
| | | | | | - Tiago Pugliese Branco
- Universidade de São Paulo, Instituto do Câncer do Estado de São Paulo, São Paulo, SP, Brasil
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19
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Navarro JG, Yang SJ, Kang I, Choi GH, Han DH, Kim KS, Choi JS. What are the most important predictive factors for clinically relevant posthepatectomy liver failure after right hepatectomy for hepatocellular carcinoma? Ann Surg Treat Res 2020; 98:62-71. [PMID: 32051814 PMCID: PMC7002877 DOI: 10.4174/astr.2020.98.2.62] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2019] [Revised: 11/07/2019] [Accepted: 01/04/2020] [Indexed: 02/06/2023] Open
Abstract
Purpose The risk of posthepatectomy liver failure (PHLF) after right hepatectomy remains substantial. Additional parameters such as computed tomography volumetry, liver stiffness measurement by FibroScan, indocyanine green retention rate at 15 minutes, and platelet count used to properly assess future liver remnant volume quality and quantity are of the utmost importance. Thus, we compared the usefulness of these modalities for predicting PHLF among patients with hepatocellular carcinoma after right hepatectomy. Methods We retrospectively reviewed patients who underwent right hepatectomy for hepatocellular carcinoma between 2007 and 2013. PHLF was determined according to International Study Group of Liver Surgery consensus definition and severity grading. Grades B and C were defined as clinically relevant posthepatectomy liver failure (CRPHLF). The results were internally validated using a cohort of 97 patients. Results Among the 90 included patients, 15 (16.7%) had CRPHLF. Multivariate analysis confirmed that platelet count < 140 (109/L) (hazard ratio [HR], 24.231; 95% confidence interval [CI], 3.623–161.693; P = 0.001) and remnant liver volume-to-body weight (RVL/BW) ratio < 0.55 (HR, 25.600; 95% CI, 4.185–156.590; P < 0.001) were independent predictors of CRPHLF. Among the 12 patients with a platelet count < 140 (109/L) and RLV/BW ratio < 0.55, 9 (75%) had CRPHLF. Likewise, 5 of 38 (13.2%) with only one risk factor developed CRPHL versus 1 of 40 (2.5%) with no risk factors. These findings were confirmed by the validation cohort. Conclusion RLV/BW ratio and platelet count are more important than the conventional RLV/TFLV, indocyanine green retention rate at 15 minutes, and liver stiffness measurement in the preoperative risk assessment for CRPHLF.
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Affiliation(s)
- Jonathan Geograpo Navarro
- Department of Surgery, Yonsei University College of Medicine, Seoul, Korea.,Division of Surgical Oncology, Department of Surgery, Vicente Sotto Memorial Medical Center, Cebu, the Philippines
| | - Seok Jeong Yang
- Department of Surgery, Yonsei University College of Medicine, Seoul, Korea
| | - Incheon Kang
- Department of Surgery, Yonsei University College of Medicine, Seoul, Korea
| | - Gi Hong Choi
- Department of Surgery, Yonsei University College of Medicine, Seoul, Korea
| | - Dai Hoon Han
- Department of Surgery, Yonsei University College of Medicine, Seoul, Korea
| | - Kyung Sik Kim
- Department of Surgery, Yonsei University College of Medicine, Seoul, Korea
| | - Jin Sub Choi
- Department of Surgery, Yonsei University College of Medicine, Seoul, Korea
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20
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Hobeika C, Ronot M, Beaufrere A, Paradis V, Soubrane O, Cauchy F. Metabolic syndrome and hepatic surgery. J Visc Surg 2019; 157:231-238. [PMID: 31866269 DOI: 10.1016/j.jviscsurg.2019.11.004] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
In Europe, the prevalence of metabolic syndrome (MS) has reached the endemic rate of 25%. Non-alcoholic fatty liver disease (NAFLD) is the hepatic manifestation of MS. Its definition is histological, bringing together the different lesions associated with hepatic steatosis (fat deposits on more than 5% of hepatocytes) without alcohol consumption and following exclusion of other causes. MS and NAFLD are implicated in the carcinogenesis of hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC). At present, HCC and ICC involving MS represent 15-20% and 20-30% respectively of indications for hepatic resection in HCC and ICC. Moreover, in the industrialized nations NAFLD is tending to become the most frequent indication for liver transplantation. MS patients combine the operative risk associated with their general condition and comorbidities and the risk associated with the presence and/or severity of NAFLD. Following hepatic resection in cases of HCC and ICC complicating MS, the morbidity rate ranges from 20 to 30%, and due to cardiovascular and infectious complications, post-transplantation mortality is heightened. The operative risk incurred by MS patients necessitates appropriate management including: (i) precise characterization of the subjacent liver; (ii) an accurately targeted approach privileging detection and optimization of treatment taking into account the relevant cardiovascular risk factors; (iii) a surgical strategy adapted to the histology of the underlying liver, with optimization of the volume of the remaining (postoperative) liver.
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Affiliation(s)
- C Hobeika
- Service de chirurgie hépato-bilio-pancréatique et transplantation hépatique, Hôpital Beaujon, AP-HP et Université de Paris, 100, boulevard du Général Leclerc, 92110, Clichy, France
| | - M Ronot
- Service de radiologie, Hôpital Beaujon, AP-HP et Université de Paris, 100, boulevard du Général Leclerc, 92110, Clichy, France
| | - A Beaufrere
- Service d'anatomo-pathologie, Hôpital Beaujon, AP-HP et Université de Paris, 100, boulevard du Général Leclerc, 92110, Clichy, France
| | - V Paradis
- Service d'anatomo-pathologie, Hôpital Beaujon, AP-HP et Université de Paris, 100, boulevard du Général Leclerc, 92110, Clichy, France
| | - O Soubrane
- Service de chirurgie hépato-bilio-pancréatique et transplantation hépatique, Hôpital Beaujon, AP-HP et Université de Paris, 100, boulevard du Général Leclerc, 92110, Clichy, France
| | - F Cauchy
- Service de chirurgie hépato-bilio-pancréatique et transplantation hépatique, Hôpital Beaujon, AP-HP et Université de Paris, 100, boulevard du Général Leclerc, 92110, Clichy, France.
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21
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Kong FH, Miao XY, Zou H, Xiong L, Wen Y, Chen B, Liu X, Zhou JJ. End-stage liver disease score and future liver remnant volume predict post-hepatectomy liver failure in hepatocellular carcinoma. World J Clin Cases 2019; 7:3734-3741. [PMID: 31799298 PMCID: PMC6887604 DOI: 10.12998/wjcc.v7.i22.3734] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/03/2019] [Revised: 10/18/2019] [Accepted: 10/30/2019] [Indexed: 02/05/2023] Open
Abstract
BACKGROUND Hepatocellular carcinoma (HCC) is the world's sixth most common malignant tumor and the third cause of cancer death. Although great progress has been made in hepatectomy, it is still associated with a certain degree of risk of post-hepatectomy liver failure (PHLF), which extends the length of hospital stay and remains the leading cause of postoperative death. Studies have shown that assessment of hepatic functional reserve before hepatectomy is beneficial for reducing the incidence of PHLF. AIM To assess the value of model for end-stage liver disease (MELD) score combined with standardized future liver remnant (sFLR) volume in predicting PHLF in patients undergoing hepatectomy for HCC. METHODS This study was attended by 238 patients with HCC who underwent hepatectomy between January 2015 and January 2018. Discrimination of sFLR volume, MELD score, and sFLR/MELD ratio to predict PHLF was evaluated according to the area under the receiver operating characteristic curve. RESULTS The patients were divided into two groups according to whether PHLF occurred after hepatectomy. The incidence of PHLF was 8.4% in our research. The incidence of PHLF increased with the decrease in sFLR volume and the increase in MELD score. Both sFLR volume and MELD score were considered independent predictive factors for PHLF. Moreover, the cut-off value of the sFLR/MELD score to predict PHLF was 0.078 (P < 0.001). This suggests that an sFLR/MELD ≥ 0.078 indicates a higher incidence of PHLF than an sFLR/MELD < 0.078. CONCLUSION MELD combined with sFLR is a reliable and effective PHLF predictor, which is superior to MELD score or sFLR volume alone.
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Affiliation(s)
- Fan-Hua Kong
- Department of General Surgery, The Second Xiangya Hospital, Central South University, Changsha 410011, Hunan Province, China
| | - Xiong-Ying Miao
- Department of General Surgery, The Second Xiangya Hospital, Central South University, Changsha 410011, Hunan Province, China
| | - Heng Zou
- Department of General Surgery, The Second Xiangya Hospital, Central South University, Changsha 410011, Hunan Province, China
| | - Li Xiong
- Department of General Surgery, The Second Xiangya Hospital, Central South University, Changsha 410011, Hunan Province, China
| | - Yu Wen
- Department of General Surgery, The Second Xiangya Hospital, Central South University, Changsha 410011, Hunan Province, China
| | - Bo Chen
- Department of General Surgery, The Second Xiangya Hospital, Central South University, Changsha 410011, Hunan Province, China
| | - Xi Liu
- Department of General Surgery, The Second Xiangya Hospital, Central South University, Changsha 410011, Hunan Province, China
| | - Jiang-Jiao Zhou
- Department of General Surgery, The Second Xiangya Hospital, Central South University, Changsha 410011, Hunan Province, China
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22
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Yang Y, Yao JH, Du QY, Zhou YC, Yao TJ, Wu Q, Liu J, Ou YR. Connexin 32 downregulation is critical for chemoresistance in oxaliplatin-resistant HCC cells associated with EMT. Cancer Manag Res 2019; 11:5133-5146. [PMID: 31213923 PMCID: PMC6549660 DOI: 10.2147/cmar.s203656] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2019] [Accepted: 04/16/2019] [Indexed: 12/25/2022] Open
Abstract
Background: Oxaliplatin (OXA)-based chemotherapy is critical in the management of advanced hepatocellular carcinoma (HCC); however, acquired drug resistance has largely restricted its clinical efficacy. This study aims to explore the key mechanisms and regulatory factors determining chemosensitivity in HCC. Methods: We developed OXA-resistant (OR) HCC cells and used multiple methods, including real-time RT-PCR, Western blot, immunofluorescence, transwell invasion assay, wound-healing assay, MTT assay, gene transfection, and immunohistochemistry to achieve our goals. Results: We found that OR HCC cells showed a typical epithelial–mesenchymal transition (EMT) phenotype. Meanwhile, the expression of Cx32, a major member of the liver connexin (Cx) family, was lowly expressed in OR HCC cells. Downregulation of Cx32 in parental HCC cells led to EMT induction and thereby reduced OXA cytotoxicity, while Cx32 upregulation in OR HCC cells could reverse the EMT phenotype and partially restore chemosensitivity to OXA. Finally, in human HCC tissue samples, Cx32 was positively correlated with the expression of the EMT marker E-cadherin and negatively correlated with the expression of Vimentin. Conclusion: Our findings demonstrated that downregulation of Cx32 may be an important determinant for HCC cells to acquire EMT-related acquired drug resistance to OXA, and targeting Cx32 could be a novel strategy to overcome OXA resistance in HCC.
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Affiliation(s)
- Yan Yang
- Department of Medical Oncology, The First Affiliated Hospital of Bengbu Medical College, Bengbu 233004, People's Republic of China
| | - Jing-Hao Yao
- Department of Medical Oncology, The First Affiliated Hospital of Bengbu Medical College, Bengbu 233004, People's Republic of China
| | - Qian-Yu Du
- Department of Medical Oncology, The First Affiliated Hospital of Bengbu Medical College, Bengbu 233004, People's Republic of China
| | - Yong-Chun Zhou
- Department of Radiation Oncology, The First Affiliated Hospital of Bengbu Medical College, Bengbu 233004, People's Republic of China
| | - Ting-Jing Yao
- Department of Surgical Oncology, The First Affiliated Hospital of Bengbu Medical College, Bengbu 233004, People's Republic of China
| | - Qiong Wu
- Department of Pathology, The First Affiliated Hospital of Bengbu Medical College, Bengbu 233004, People's Republic of China
| | - Jing Liu
- Department of Medical Oncology, The First Affiliated Hospital of Bengbu Medical College, Bengbu 233004, People's Republic of China
| | - Yu-Rong Ou
- Department of Pathology, The First Affiliated Hospital of Bengbu Medical College, Bengbu 233004, People's Republic of China
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23
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Wang X, Chen M, Wei R, Wang Z. External Radiation versus Internal Radiation for Patients with Advanced Unresectable HCC -A SEER Based Study. J Cancer 2019; 10:1171-1180. [PMID: 30854126 PMCID: PMC6400665 DOI: 10.7150/jca.28983] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/03/2018] [Accepted: 12/05/2018] [Indexed: 12/19/2022] Open
Abstract
Hepatocellular carcinoma (HCC), 2nd most lethal cancer globally, is the major type of primary liver malignancies currently resulting in about 800,000 deaths globally per annum. Surgical resection remains the only curative treatment to HCC, which does not fit for many patients diagnosed with advanced HCC. Radiation therapy has been gradually concerned as an optional treatment for patients with advanced unresectable HCC. This study aimed to compare external radiation (beam radiation) and internal radiation as a single radiation therapy to advanced HCC patients (TNA stage III and IV according to the derived AJCC Stage, 6th edition) stratified by other risk factors, based on the data collected from the Surveillance, Epidemiology and End Results (SEER) national database. In this cohort study, we mainly clarified the following three points: 1. Choices of radiation therapy for advanced HCC patients vary in demographic and clinical factors. Among these, TNM classification is the key factor. 2. Internal radiation provides a better prognosis in both OS and CSS. 3. Patients in stage IV could benefit from internal radiation preferentially, while for patients in stage III, internal radiation therapy makes no difference compared with external radiation.
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Affiliation(s)
| | | | | | - Zheng Wang
- ✉ Corresponding author: Zheng Wang, MD, Department of General Surgery, Huashan Hospital & Cancer Metastasis Institute, Fudan university, 12 Urumqi Road (M), Shanghai 200040, P.R. China. Tel: & Fax: +86-21-5288-7172; E-mail:
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24
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Tustumi F, Ernani L, Coelho FF, Bernardo WM, Junior SS, Kruger JAP, Fonseca GM, Jeismann VB, Cecconello I, Herman P. Preoperative strategies to improve resectability for hepatocellular carcinoma: a systematic review and meta-analysis. HPB (Oxford) 2018; 20:1109-1118. [PMID: 30057123 DOI: 10.1016/j.hpb.2018.06.1798] [Citation(s) in RCA: 40] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/01/2018] [Revised: 06/14/2018] [Accepted: 06/16/2018] [Indexed: 02/06/2023]
Abstract
BACKGROUND Preoperative strategies to increase the future liver remnant are useful methods to improve resectability rates for patients with hepatocellular carcinoma (HCC). The aim of this study was to perform a systematic review and meta-analysis of the main strategies used for this purpose. METHODS A systematic review was performed in PubMed, EMBASE, Cochrane and Scielo/LILACS. The procedures included for analysis were portal vein embolization or ligation (PVE/PVL), sequential transarterial embolization and PVE (TACE + PVE), radioembolization (RE) and associated liver partition and portal vein ligation for staged hepatectomy (ALPPS). Perioperative morbidity and mortality, post-hepatectomy liver failure (PHLF), and survival rates were evaluated. RESULTS A total of 46 studies were included in the systematic review (1284 patients). Resection rate was higher in TACE + PVE (90%; N = 315) when compared to PVE/PVL (75%; N = 254; P = <0.001) and similar to ALPPS (84%; N = 43; P = 0.374) and RE (100%; N = 28; P = 0.14). ALPPS was associated with higher PHLF and perioperative mortality rates when compared to PVE/PVL and TACE + PVE. ALPPS and RE showed higher risk of major complications than PVE/PVL and TACE + PVE. CONCLUSION Preoperative strategies to increase liver volume are effective in achieving resectability of HCC. TACE + PVE is as safe as PVL/PVE providing higher OS. ALPPS is associated with a higher risk of PHLF, major complications, and mortality. RE despite the small experience seems to present similar resection rate and OS as TACE + PVE with higher rate of major complications.
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Affiliation(s)
- Francisco Tustumi
- Department of Gastroenterology, Digestive Surgery Division, Sao Paulo School of Medicine, Brazil.
| | - Lucas Ernani
- Department of Gastroenterology, Digestive Surgery Division, Sao Paulo School of Medicine, Brazil
| | - Fabricio F Coelho
- Department of Gastroenterology, Digestive Surgery Division, Sao Paulo School of Medicine, Brazil
| | - Wanderley M Bernardo
- Department of Gastroenterology, Digestive Surgery Division, Sao Paulo School of Medicine, Brazil
| | - Sérgio S Junior
- Department of Gastroenterology, Digestive Surgery Division, Sao Paulo School of Medicine, Brazil
| | - Jaime A P Kruger
- Department of Gastroenterology, Digestive Surgery Division, Sao Paulo School of Medicine, Brazil
| | - Gilton M Fonseca
- Department of Gastroenterology, Digestive Surgery Division, Sao Paulo School of Medicine, Brazil
| | - Vagner B Jeismann
- Department of Gastroenterology, Digestive Surgery Division, Sao Paulo School of Medicine, Brazil
| | - Ivan Cecconello
- Department of Gastroenterology, Digestive Surgery Division, Sao Paulo School of Medicine, Brazil
| | - Paulo Herman
- Department of Gastroenterology, Digestive Surgery Division, Sao Paulo School of Medicine, Brazil
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25
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De Raffele E, Mirarchi M, Cuicchi D, Lecce F, Ricci C, Casadei R, Cola B, Minni F. Simultaneous curative resection of double colorectal carcinoma with synchronous bilobar liver metastases. World J Gastrointest Oncol 2018; 10:293-316. [PMID: 30364774 PMCID: PMC6198303 DOI: 10.4251/wjgo.v10.i10.293] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/09/2018] [Revised: 07/28/2018] [Accepted: 08/21/2018] [Indexed: 02/05/2023] Open
Abstract
Synchronous colorectal carcinoma (SCRC) indicates more than one primary colorectal carcinoma (CRC) discovered at the time of initial presentation, accounts for 3.1%-3.9% of CRC, and may occur either in the same or in different colorectal segments. The accurate preoperative diagnosis of SCRC is difficult and diagnostic failures may lead to inappropriate treatment and poorer prognosis. SCRC requires colorectal resections tailored to individual patients, based on the number, location, and stage of the tumours, from conventional or extended hemicolectomies to total colectomy or proctocolectomy, when established predisposing conditions exist. The overall perioperative risks of surgery for SCRC seem to be higher than for solitary CRC. Simultaneous colorectal and liver resection represents an appealing surgical strategy in selected patients with CRC and synchronous liver metastases (CRLM), even though the cumulative risks of the two procedures need to be adequately evaluated. Simultaneous resections have the noticeable advantage of avoiding a second laparotomy, give the opportunity of an earlier initiation of adjuvant therapy, and may significantly reduce the hospital costs. Because an increasing number of recent studies have shown good results, with morbidity, perioperative hospitalization, and mortality rates comparable to staged resections, simultaneous procedures can be selectively proposed even in case of complex colorectal resections, including those for SCRC and rectal cancer. However, in patients with multiple bilobar CRLM, major hepatectomies performed simultaneously with colorectal resection have been associated with significant perioperative risks. Conservative or parenchymal-sparing hepatectomies reduce the extent of hepatectomy while preserving oncological radicality, and may represent the best option for selected patients with multiple CRLM involving both liver lobes. Parenchymal-sparing liver resection, instead of major or two-stage hepatectomy for bilobar disease, seemingly reduces the overall operative risk of candidates to simultaneous colorectal and liver resection, and may represent the most appropriate surgical strategy whenever possible, also for patients with advanced SCRC and multiple bilobar liver metastases.
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Affiliation(s)
- Emilio De Raffele
- Unità Operativa di Chirurgia Generale, Dipartimento dell’Apparato Digerente, Azienda Ospedaliero-Universitaria di Bologna, Policlinico S.Orsola-Malpighi, Bologna 40138, Italy
| | - Mariateresa Mirarchi
- U.O. di Chirurgia Generale, Dipartimento Strutturale Chirurgico, Ospedale “Antonio e Margherita, ” Tortona (AL) 15057, Italy
| | - Dajana Cuicchi
- Unità Operativa di Chirurgia Generale, Dipartimento dell’Apparato Digerente, Azienda Ospedaliero-Universitaria di Bologna, Policlinico S.Orsola-Malpighi, Bologna 40138, Italy
| | - Ferdinando Lecce
- Unità Operativa di Chirurgia Generale, Dipartimento dell’Apparato Digerente, Azienda Ospedaliero-Universitaria di Bologna, Policlinico S.Orsola-Malpighi, Bologna 40138, Italy
| | - Claudio Ricci
- Unità Operativa di Chirurgia Generale, Dipartimento dell’Apparato Digerente, Azienda Ospedaliero-Universitaria di Bologna, Policlinico S.Orsola-Malpighi, Bologna 40138, Italy
| | - Riccardo Casadei
- Unità Operativa di Chirurgia Generale, Dipartimento dell’Apparato Digerente, Azienda Ospedaliero-Universitaria di Bologna, Policlinico S.Orsola-Malpighi, Bologna 40138, Italy
| | - Bruno Cola
- Dipartimento di Scienze Mediche e Chirurgiche (DIMEC), Alma Mater Studiorum, Policlinico S.Orsola-Malpighi, University of Bologna, Bologna 40138, Italy
| | - Francesco Minni
- Unità Operativa di Chirurgia Generale, Dipartimento dell’Apparato Digerente, Azienda Ospedaliero-Universitaria di Bologna, Policlinico S.Orsola-Malpighi, Bologna 40138, Italy
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26
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Lai HC, Yeh CC, Jeng LB, Huang SF, Liao PY, Lei FJ, Cheng WC, Hsu CL, Cai X, Chang C, Ma WL. Androgen receptor mitigates postoperative disease progression of hepatocellular carcinoma by suppressing CD90+ populations and cell migration and by promoting anoikis in circulating tumor cells. Oncotarget 2018; 7:46448-46465. [PMID: 27340775 PMCID: PMC5216809 DOI: 10.18632/oncotarget.10186] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2015] [Accepted: 05/28/2016] [Indexed: 02/06/2023] Open
Abstract
Purpose Although hepatectomy and liver transplantation surgery for hepatocellular carcinoma (HCC) are effective treatment modalities, the risk of recurrence remains high, particularly in patients with a high number of circulating tumor cells (CTCs) expressing cancer stem/progenitor cell markers. Androgen receptor (AR) signaling has been shown to suppress HCC metastasis in rodent models of HCC. In this study, we investigated whether AR is associated with postoperative HCC recurrence. Experimental Design CTCs were obtained from patients with HCC who had undergone hepatectomy to investigate whether they are associated with disease outcome. AR knockout was introduced in two mouse models of spontaneous HCC (carcinogen- and hepatitis B virus-related HCC) to delineate the role that AR plays in HCC recurrence. Biological systems analysis was used to investigate the cellular and molecular mechanisms. Results We found that the expression of AR in CTCs was negatively associated with HCC recurrence/progression after hepatectomy. Our results suggest that AR-mediated suppression of HCC recurrence/progression is governed by a three-pronged mechanism. First, AR suppresses the expression of CD90 in CTCs by upregulating Histone 3H2A. Second, AR suppresses cell migration at the transcriptome level. Third, AR promotes anoikis of CTCs via dysregulation of cytoskeletal adsorption. Conclusions The results indicate that AR expression may be the gatekeeper of postoperative HCC recurrence. Therefore, targeting AR in presurgical down-staging procedures may serve as a secondary prevention measure against HCC recurrence in the future.
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Affiliation(s)
- Hsueh-Chou Lai
- Graduate Institution of Clinical Medical Science, and Graduate Institution of Cancer Biology, China Medical University, Taichung 40403, Taiwan.,Sex Hormone Research Center, Organ Transplantation Center, Research Center for Tumor Medical Science, and Department of Gastroenterology, China Medical University/Hospital, Taichung 40403, Taiwan
| | - Chun-Chieh Yeh
- Graduate Institution of Clinical Medical Science, and Graduate Institution of Cancer Biology, China Medical University, Taichung 40403, Taiwan.,Sex Hormone Research Center, Organ Transplantation Center, Research Center for Tumor Medical Science, and Department of Gastroenterology, China Medical University/Hospital, Taichung 40403, Taiwan
| | - Long-Bin Jeng
- Graduate Institution of Clinical Medical Science, and Graduate Institution of Cancer Biology, China Medical University, Taichung 40403, Taiwan
| | - Shang-Fen Huang
- Sex Hormone Research Center, Organ Transplantation Center, Research Center for Tumor Medical Science, and Department of Gastroenterology, China Medical University/Hospital, Taichung 40403, Taiwan
| | - Pei-Ying Liao
- Sex Hormone Research Center, Organ Transplantation Center, Research Center for Tumor Medical Science, and Department of Gastroenterology, China Medical University/Hospital, Taichung 40403, Taiwan
| | - Fu-Ju Lei
- Graduate Institution of Clinical Medical Science, and Graduate Institution of Cancer Biology, China Medical University, Taichung 40403, Taiwan.,Sex Hormone Research Center, Organ Transplantation Center, Research Center for Tumor Medical Science, and Department of Gastroenterology, China Medical University/Hospital, Taichung 40403, Taiwan
| | - Wei-Chun Cheng
- Graduate Institution of Clinical Medical Science, and Graduate Institution of Cancer Biology, China Medical University, Taichung 40403, Taiwan.,Sex Hormone Research Center, Organ Transplantation Center, Research Center for Tumor Medical Science, and Department of Gastroenterology, China Medical University/Hospital, Taichung 40403, Taiwan
| | - Cheng-Lung Hsu
- Division of Hematology-Oncology, Department of Internal Medicine, Chang Gung University/Memorial Hospital, Taoyuan 333, Taiwan
| | - Xiujun Cai
- Chawnshang Chang Liver Cancer Center, Department of General Surgery, Sir Run-Run Shaw Hospital, Zhejiang University, Hangzhou 310016, China
| | - Chawnshang Chang
- Sex Hormone Research Center, Organ Transplantation Center, Research Center for Tumor Medical Science, and Department of Gastroenterology, China Medical University/Hospital, Taichung 40403, Taiwan.,Chawnshang Chang Liver Cancer Center, Department of General Surgery, Sir Run-Run Shaw Hospital, Zhejiang University, Hangzhou 310016, China.,George Whipple Laboratory for Cancer Research, Department of Pathology, The Wilmot Cancer Center, University of Rochester Medical Center, Rochester, NY 14623, USA
| | - Wen-Lung Ma
- Graduate Institution of Clinical Medical Science, and Graduate Institution of Cancer Biology, China Medical University, Taichung 40403, Taiwan.,Sex Hormone Research Center, Organ Transplantation Center, Research Center for Tumor Medical Science, and Department of Gastroenterology, China Medical University/Hospital, Taichung 40403, Taiwan
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27
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Yang Y, Zhang N, Zhu J, Hong XT, Liu H, Ou YR, Su F, Wang R, Li YM, Wu Q. Downregulated connexin32 promotes EMT through the Wnt/β-catenin pathway by targeting Snail expression in hepatocellular carcinoma. Int J Oncol 2017; 50:1977-1988. [PMID: 28498415 PMCID: PMC5435329 DOI: 10.3892/ijo.2017.3985] [Citation(s) in RCA: 29] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2017] [Accepted: 04/19/2017] [Indexed: 12/16/2022] Open
Abstract
Hepatocellular carcinoma (HCC) is one of the common malignances in the world and is associated with high mortality and poor prognosis, partly due to early invasion and metastasis. Cx32 has been indicated to be involved in the progression of many cancers including HCC, but its relationship with tumor invasion and metastasis is still controversial. In the present study, the downregulated Cx32 in HCC tissue was found negatively correlated with histological grade and lymph node metastasis. Cx32 regulated HCC migration and invasion in vitro and inhibited tumor metastasis in xenograft models in vivo. We subsequently identified that Cx32 mediated epithelial-mesenchymal transition (EMT) by regulating Snail expression, and the enhanced Snail was due to activation of Wnt/β-catenin signaling in response to Cx32 inhibition. Finally, decreased expression of Cx32 showed strong correlation with loss/reduction of E-cadherin, higher expression of Snail, and nuclear accumulation of β-catenin in HCC tissues. Taken together, our results suggest that Cx32 inhibits HCC invasion and metastasis through Snail-mediated EMT, Cx32 and this signaling pathway molecules may offer potential targets for HCC cancer therapy.
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Affiliation(s)
| | | | - Jian Zhu
- Department of Cardiovasology, The First Affiliated Hospital of Bengbu Medical College, Bengbu, Anhui 233004
| | - Xiao-Ting Hong
- Cancer Research Center, Department of Basic Medical Sciences, Medical College, Xiamen University, Xiamen, Fujian 361102
| | - Hao Liu
- Department of Pharmacy, Bengbu Medical College, Bengbu, Anhui 233000, P.R. China
| | | | - Fang Su
- Departments of Medical Oncology
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Magistri P, Tarantino G, Guidetti C, Assirati G, Olivieri T, Ballarin R, Coratti A, Di Benedetto F. Laparoscopic versus robotic surgery for hepatocellular carcinoma: the first 46 consecutive cases. J Surg Res 2017. [PMID: 28641762 DOI: 10.1016/j.jss.2017.05.005] [Citation(s) in RCA: 42] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
BACKGROUND Hepatocellular carcinoma has a growing incidence worldwide, and represents a leading cause of death in patients with cirrhosis. Nowadays, minimally invasive approaches are spreading in every field of surgery and in liver surgery as well. MATERIALS AND METHODS We retrospectively reviewed demographics, clinical, and pathologic characteristics and short-term outcomes of patients who had undergone minimally invasive resections for hepatocellular carcinoma at our institution between June 2012 and May 2016. RESULTS No significant differences in demographics and comorbidities were found between patients in the laparoscopic (n = 24) and robotic (n = 22) groups, except for the rates of cirrhotic patients (91.7% and 68.2%, respectively, P = 0.046). Perioperative data analysis showed that the operative time (mean, 211 and 318 min, respectively, P < 0.001) was the only parameter in favor of laparoscopy. Conversely, robotic-assisted resections were related to less Clavien I-II postoperative complications (22 cases versus 13 cases; P = 0.03). As regards resection margins, the two groups were similar with no statistically significant differences in rates of disease-free resection margins. CONCLUSIONS A modern hepatobiliary center should offer both open and minimally invasive approaches to liver disease to provide the best care for each patient, according to the individual comorbidities, risk factors, and personal quality of life expectations. Our results show that the robotic approach is a reliable tool for accurate oncologic surgery, comparable to the laparoscopic approach. Robotic surgery also allows the surgeon to safely approach liver segments that are difficult to resect in laparoscopy, namely segments I-VII-VIII.
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Affiliation(s)
- Paolo Magistri
- Hepato-Pancreato-Biliary Surgery and Liver Transplantation Unit, University of Modena and Reggio Emilia, Modena, Italy; Department of Medical and Surgical Sciences and Translational Medicine, Faculty of Medicine and Psychology, Sapienza - University of Rome, Rome, Italy
| | - Giuseppe Tarantino
- Hepato-Pancreato-Biliary Surgery and Liver Transplantation Unit, University of Modena and Reggio Emilia, Modena, Italy
| | - Cristiano Guidetti
- Hepato-Pancreato-Biliary Surgery and Liver Transplantation Unit, University of Modena and Reggio Emilia, Modena, Italy
| | - Giacomo Assirati
- Hepato-Pancreato-Biliary Surgery and Liver Transplantation Unit, University of Modena and Reggio Emilia, Modena, Italy
| | - Tiziana Olivieri
- Hepato-Pancreato-Biliary Surgery and Liver Transplantation Unit, University of Modena and Reggio Emilia, Modena, Italy
| | - Roberto Ballarin
- Hepato-Pancreato-Biliary Surgery and Liver Transplantation Unit, University of Modena and Reggio Emilia, Modena, Italy
| | - Andrea Coratti
- Division of Surgical Oncology and Robotics, Azienda Ospedaliero-Universitaria di Careggi, Florence, Italy
| | - Fabrizio Di Benedetto
- Hepato-Pancreato-Biliary Surgery and Liver Transplantation Unit, University of Modena and Reggio Emilia, Modena, Italy.
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29
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Zou H, Tao Y, Wang ZM. Integration of Child-Pugh score with future liver remnant yields improved prediction of liver dysfunction risk for HBV-related hepatocellular carcinoma following hepatic resection. Oncol Lett 2017; 13:3631-3637. [PMID: 28521464 PMCID: PMC5431318 DOI: 10.3892/ol.2017.5919] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/20/2016] [Accepted: 01/31/2017] [Indexed: 02/06/2023] Open
Abstract
Assessment of hepatic functional reserve is important to enable the selection of appropriate treatment methods and safe hepatic resection in hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC). In the present study, an evaluation was made of the clinical value of combining the Child-Pugh score (CPS) with the standardized future liver remnant (sFLR) measurement to predict postoperative liver dysfunction (PLD). A total of 61 HBV-related HCC patients undergoing liver volumetry prior to hepatectomy were enrolled in the study. The sFLR was calculated as the ratio of FLR volume to standardized liver volume. PLD was defined as a prothrombin time of >18 sec or a peak serum bilirubin level of >51.3 µmol/l for 7 days after surgery. Univariate analysis and multivariate logistic regression analysis were performed to identify risk factors associated with PLD. The correlation between PLD and the combination of sFLR and CPS was analyzed. In total, 18 out of 61 patients developed PLD (29.5%), with a significantly higher PLD incidence for a CPS of 6 than a CPS of 5 (P<0.05). Multivariate logistic regression analysis revealed that a prothrombin time of <13.3 sec and an sFLR of <0.55 were independent risk factors for PLD. Receiver operating characteristic (ROC) curve analysis revealed that the cut-off values of sFLR and sFLR/CPS for predicting PLD were 54.5% and 0.0916, respectively, with areas under the ROC curve of 0.820 and 0.860, respectively. The combination of CPS and sFLR appears to yield improved prediction of the occurrence of PLD compared with either CPS or sFLR alone.
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Affiliation(s)
- Heng Zou
- Department of Hepatobiliary Surgery, Xiangya Hospital, Central South University, Changsha, Hunan 410008, P.R. China
| | - Yiming Tao
- Department of Hepatobiliary Surgery, Xiangya Hospital, Central South University, Changsha, Hunan 410008, P.R. China
| | - Zhi-Ming Wang
- Department of Hepatobiliary Surgery, Xiangya Hospital, Central South University, Changsha, Hunan 410008, P.R. China
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30
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She WH, Chok KS. Strategies to increase the resectability of hepatocellular carcinoma. World J Hepatol 2015; 7:2147-2154. [PMID: 26328026 PMCID: PMC4550869 DOI: 10.4254/wjh.v7.i18.2147] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/27/2015] [Revised: 08/10/2015] [Accepted: 08/20/2015] [Indexed: 02/06/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is best treated by liver transplantation, but the applicability of transplantation is greatly limited. Tumor resection in partial hepatectomy is hence resorted to. However, in most parts of the world, only 20%-30% of HCCs are resectable. The main reason for such a low resectability is a future liver remnant too small to be sufficient for the patient. To allow more HCC patients to undergo curative hepatectomy, a variety of ways have been developed to increase the resectability of HCC, mainly ways to increase the future liver remnants in patients through hypertrophy. They include portal vein embolization, sequential transarterial chemoembolization and portal vein embolization, staged hepatectomy, two-staged hepatectomy with portal vein ligation, and Associating Liver Partition and Portal Vein Ligation in Staged Hepatectomy. Herein we review, describe and evaluate these different ways, ways that can be life-saving.
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Affiliation(s)
- Wong Hoi She
- Wong Hoi She, Kenneth SH Chok, Department of Surgery, the University of Hong Kong, Hong Kong, China
| | - Kenneth Sh Chok
- Wong Hoi She, Kenneth SH Chok, Department of Surgery, the University of Hong Kong, Hong Kong, China
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31
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Yuan SX, Zhang J, Xu QG, Yang Y, Zhou WP. Long noncoding RNA, the methylation of genomic elements and their emerging crosstalk in hepatocellular carcinoma. Cancer Lett 2015; 379:239-44. [PMID: 26282784 DOI: 10.1016/j.canlet.2015.08.008] [Citation(s) in RCA: 36] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/04/2015] [Revised: 07/30/2015] [Accepted: 08/07/2015] [Indexed: 02/06/2023]
Abstract
The epigenetic mechanism that incorporates DNA methylation alterations, histone modifications, and non-coding RNA expression has been identified as a major characteristic in distinguishing physiological and pathological settings of cancers including hepatocellular carcinoma (HCC), the third leading cause of mortality related cancer. The advance in methylation modification of chromatin elements (for both genomic DNA and histone tails) and the emerging roles of long noncoding RNA (lncRNA) have given us a better understanding of molecular mechanisms underlying HCC. Recently, methods like genome-wide lncRNA profiling and histone hallmark detection were reported to discover mass tumor-associated lncRNAs epigenetically deregulated by differential chromosome modification, mainly by genomic DNA and histone methylation. Therefore, aberrant methylation modification of certain particular lncRNA genes could be crucial events correlating with unfavorable outcomes in HCC. In addition, amount of lncRNAs could act as a manipulator for DNA methylation or a scaffold for histone modification to affect key signaling pathways in hepatocarcinogenesis. This suggests that methylation modification of chromatin elements may have functional crosstalk with lncRNA. Here, we aim to outline the emerging role of the methylation and lncRNA, and their crosstalk of molecular mechanism.
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Affiliation(s)
- Sheng-Xian Yuan
- The Third Department of Hepatic Surgery, Eastern Hepatobiliary Hospital, Second Military Medical University, Shanghai, China
| | - Jin Zhang
- The Third Department of Hepatic Surgery, Eastern Hepatobiliary Hospital, Second Military Medical University, Shanghai, China
| | - Qing-Guo Xu
- The Third Department of Hepatic Surgery, Eastern Hepatobiliary Hospital, Second Military Medical University, Shanghai, China
| | - Yuan Yang
- The Third Department of Hepatic Surgery, Eastern Hepatobiliary Hospital, Second Military Medical University, Shanghai, China
| | - Wei-Ping Zhou
- The Third Department of Hepatic Surgery, Eastern Hepatobiliary Hospital, Second Military Medical University, Shanghai, China.
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32
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Harlan LC, Parsons HM, Wiggins CL, Stevens JL, Patt YZ. Treatment of hepatocellular carcinoma in the community: disparities in standard therapy. Liver Cancer 2015; 4:70-83. [PMID: 26020030 PMCID: PMC4439839 DOI: 10.1159/000367729] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023] Open
Abstract
BACKGROUND AND AIMS Hepatocellular carcinoma (HCC) incidence is expected to rise dramatically over the next decades because of increasing hepatitis C infections and obesity-related comorbidities. However, little information exists regarding the treatment of patients with HCC in the community setting. The purpose of this article was to characterize patterns of diagnosis, treatment, and survival for HCC in the community. METHODS We identified 946 HCC patients in the 2007 National Cancer Institute's Patterns of Care study. Chi-square analyses and multivariable regression were used to examine patient and provider factors associated with treatment and survival by stage at diagnosis. RESULTS Our primary findings indicate that liver transplants, embolization, or radiofrequency ablation for Barcelona Clinic Liver Cancer stage A patients were performed significantly less often for non-Hispanic blacks, Hispanics, patients in the highest income quartile, and patients with Medicaid. Patients with stage D disease were less likely to receive cancer therapy if they had Medicaid insurance compared to private insurance (p<0.001 for all). In multivariable analyses, all-cause mortality was associated with treatment in a hospital without a residency training program (hazard ratio [HR] 1.4 [1.1,1.9]), more advanced stage (HR: 10.6 [5.7, 19.5] stage D vs. A), and lack of appropriate treatment (HR: 2.4 [1.9,3.2]). CONCLUSIONS This is the first population-based study to evaluate therapy provided for HCC in the community. Current therapy depended on patients' HCC stage at diagnosis and other clinical and demographic factors. Overall, our study identifies those least likely to receive specific therapies in a variety of health care settings and can inform strategies for promoting appropriate therapy now and as new agents are developed.
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Affiliation(s)
- Linda C. Harlan
- Division of Cancer Control and Population Sciences, National Cancer Institute, Bethesda, Md., USA,*Linda C. Harlan, PhD NCI/ARP, Division of Cancer Control and Population Sciences, National Cancer Institute, Room 3E426 9609 Medical Center Drive, MSC 9762 Bethesda, Maryland 20892-9762 (USA), Tel. +1 240 276 6854, E-Mail
| | - Helen M. Parsons
- Department of Epidemiology and Biostatistics, University of Texas Health Science Center at San Antonio, San Antonio, Tex., USA
| | - Charles L. Wiggins
- University of New Mexico (UNM) Health Sciences Center, Albuquerque, N.M., USA
| | | | - Yehuda Z. Patt
- University of New Mexico (UNM) Health Sciences Center, Albuquerque, N.M., USA
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